Biodegradable Composite Scaffolds Research Articles

Additive manufacturing a novel bioceramic bone scaffold with MgO/Ca3(PO4)2: Microstructure, mechanical property and controllable degradation behavior

Biodegradable bone grafts have gained considerable attention in the field of clinical research as they can be used to avoid re-surgery to remove scaffolds. We fabricated biodegradable composite ceramic scaffolds using magnesium oxide and calcium phosphate following the vat photopolymerization technology. We studied the effects of different magnesium oxide content on the process of in vitro degradation of the composite scaffolds and discussed the degradation process by comparing the extent of degradation realized in Tris-HCl buffer and simulated body fluids. We also explored the variations in the mechanical properties of the scaffolds during degradation. The results revealed that the composite scaffolds maintained the strength standard for spongy bone (compressive strength σ: 2–20 MPa) even after 28 d of degradation. Additionally, the strength of the composite scaffold containing 80 wt% magnesium oxide was comparable to the strength standard recommended for cortical bones (σ: 100–200 MPa). Controllable degradation rates were recorded, and acceptable mechanical properties were observed for these scaffolds during degradation. The results reported herein can be potentially used to expand the application prospects of biodegradable scaffolds.

Comparison of Autografts and Biodegradable 3D-Printed Composite Scaffolds with Osteoconductive Properties for Tissue Regeneration in Bone Tuberculosis.

Tuberculosis remains one of the major health problems worldwide. Besides the lungs, tuberculosis affects other organs, including bones and joints. In the case of bone tuberculosis, current treatment protocols include necrectomy in combination with conventional anti-tuberculosis therapy, followed by reconstruction of the resulting bone defects. In this study, we compared autografting and implantation with a biodegradable composite scaffold for bone-defect regeneration in a tuberculosis rabbit model. Porous three-dimensional composite materials were prepared by 3D printing and consisted of poly(ε-caprolactone) filled with nanocrystalline cellulose modified with poly(glutamic acid). In addition, rabbit mesenchymal stem cells were adhered to the surface of the composite scaffolds. The developed tuberculosis model was verified by immunological subcutaneous test, real-time polymerase chain reaction, biochemical markers and histomorphological study. Infected animals were randomly divided into three groups, representing the infection control and two experimental groups subjected to necrectomy, anti-tuberculosis treatment, and plastic surgery using autografts or 3D-composite scaffolds. The lifetime observation of the experimental animals and analysis of various biochemical markers at different time periods allowed the comparison of the state of the animals between the groups. Micro-computed tomography and histomorphological analysis enabled the evaluation of osteogenesis, inflammation and cellular changes between the groups, respectively.

3D Printing of Porous Degradable Scaffolds with Polylactic Acid‐Loaded Bioactive Glass and Calcium Sulfate Hemihydrate for Bone Defect Repair

AbstractRepair of bone defects, especially critical‐sized bone defects, remains a major clinical problem, and bone nonunion is the biggest challenge. Herein, melt‐extrusion 3D printing is applied to prepare biodegradable composite scaffolds containing bioactive glass (BAG), calcium sulfate hemihydrate (CSH), and polylactic acid (PLA). The compressive strength of scaffolds is similar to that of human bone tissue. In vitro and in vivo experiments show that the scaffolds have good biocompatibility. The scaffold can maintain the biomechanical stability of the bone defect area during the follow‐up period of 20 weeks and has no damage to liver and kidney in animal experiments. Scaffold degradation is accompanied by trabecular bone and vessel neogenesis. While the PLA group and control group cannot carry out effective bone defect repair, the bone defect repair effect of the PLA‐CSH‐BAG group is satisfactory. In conclusion, the biodegradable porous scaffold has been proposed as a safe and effective approach for the repair of bone defects.

3D biodegradable shape changing composite scaffold with programmable porous structures for bone engineering

This study developed a biodegradable composite porous polyurethane scaffold based on polycaprolactone and polyethylene glycol by sequential in-situ foaming salt leaching and freeze-drying process with responsive shape changing performance. Biomineral hydroxyapatite (HA) was introduced into the polyurethane matrix as inorganic fillers. Infrared spectroscopy results proved a successful synthesis, scanning electron microscopy showed that the scaffold’s porosity decreased with the addition of HA while the average pore size increased. X-ray diffraction and differential scanning calorimetry showed that the addition of HA lowered the melting point of the scaffold, resulting in a transition temperature close to the human body temperature. From the bending experiments, it could be demonstrated that PUHA20 has excellent shape memory performance with shape fixity ratio >98.9% and shape recovery ratio >96.2%. Interestingly, the shape-changing capacity could be influenced by the porous structures with variation of HA content. The shape recovery speed was further accelerated when the material was immersed in phosphate buffered saline at 37 °C. Additionally, in vitro mineralization experiments showed that the scaffold incorporating HA had good osteoconductivity, and implantation assessment proved that scaffolds had good in vivo biocompatibility. This scaffold is a promising candidate for implantation of bone defects.

Anti-infective composite cryogel scaffold treats osteomyelitis and augments bone healing in rat femoral condyle

Bone and joint infections pose a serious challenge in the orthopedic medical condition which presents a major health care problem and economic burden to the patients. The current treatment strategies adopted have a very limited successful outcome in majority of the cases and need serious reconsiderations in terms of management, diagnosis and effective treatment approach. Herein, we have developed a composite cryogel scaffold from nanohydroxyapatite and collagen mimicking natural bone composition for the local delivery of antibiotic to treat osteomyelitis. The biomimetic and biodegradable antibiotic-loaded composite scaffold was found to be biocompatible with potent osteogenic capacity and anti-infective characteristics under in vitro conditions. Moreover, the anti-infective potency of the antibiotic-loaded composite cryogel was also evaluated in rat osteomyelitis model to cure the infection and promote bone healing. It was observed that anti-infective collagen-nanohydroxyapatite composite cryogel when loaded with bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) could completely eradicate the infection in rat femoral condyle and simultaneously, accelerate bone healing at the dead space created during surgical procedures. The approach developed in this study is the development of biomimetic and bioactive composite carrier of antibiotics for the treatment of bone infection. The findings of this study insinuate that this antibiotic-loaded composite cryogel scaffold could potentially be used as an anti-infective biomaterial for the treatment of bone infections which will simultaneosuly promote bone healing at the dead space created during surgical procedures.

Programmable, biodegradable composite scaffolds with variable pore morphology for minimal invasive bone repair

Tissue engineered biocompatible scaffolds could mimic the natural bone structure for cell adhesion and proliferation, however, patients suffer from large volume implantation. In this study, a porous composite biocompatible bone scaffold based on shape memory polymer materials (SMP) was developed from poly(ε-caprolactone) (PCL) diol, hexamethylene diisocyanate (HDI) and hydroxyapatite (HA). The prepared shape memory composite scaffold presented good pore connectivity, high porosity, good mechanical and biological properties. Additionally, after programming to a temporary shape, the scaffolds could recover to the initial shape, filling the site of bone defect. Moreover, HA improved the mechanical properties of scaffolds, promoted cell adhesion and influencing the shape recovering speed. During in vitro mineralization, HA could promote the formation and deposition of bone-like hydroxyapatite and accelerate the repair of damaged tissues, no inflammatory problem occurred after the in vivo implantations. These programmable scaffolds could be applied in minimal invasive bone repair.

Current Advances in the Roles of Doped Bioactive Metal in Biodegradable Polymer Composite Scaffolds for Bone Repair: A Mini Review

The election of bone tissue engineering scaffolds material is mainly based on the bionics of natural bones. Although the content of trace elements in bone is low, the lack of them affects the growth and metabolism of bones, thus increasing the risk of orthopedic diseases caused by the deterioration of bone quality. Therefore, inspired by trace elements in natural bone, biodegradable polymer composite scaffolds doped with bioactive metals such as Mg, Zn, Sr, Fe, Cu, Mn, Co, Li, Ag, Nb, and V have attracted more attention. Herein, the role of bioactive metals doping in biodegradable polymer matrix is mainly reviewed, including improving hydrophilicity, preventing aseptic inflammation caused by acidic degradation products, imparting antibacterial activity, improving mechanical properties, and promoting vascularization of polymer scaffolds. Then, the reasons and solutions for interfacial bonding and cytotoxicity caused by doping bioactive metals are focused on.

In vitro and mechanical characterization of PLA/egg shell biocomposite scaffold manufactured using fused deposition modeling technology for tissue engineering applications

AbstractFused deposition modeling (FDM) plays a crucial role in additive manufacturing in the development of novel materials to match the properties of patient specific implants. Polylactic acid (PLA) based biodegradable composite scaffold has shown remarkable progress in tissue engineering due to its better processing compatibility and mechanical properties. In this research work, widely available natural biomaterial egg shell particle (ESP) was used as a filler material, as the minerals aid during bone formation and mineralization. To study the effect of filler particles in PLA, filler percentage and porosity were varied up to 12% and 60%. The scaffolds were characterized for compression, surface morphology, porosity, water contact angle, and in vitro studies. Micro fibers with 10–100 μm were developed using FDM technology. A reduction of up to 85% was made in the water contact angle with respect to an increase in filler particles. 10% ESP withstood a maximum load of 369 MPa at 40% porosity. A maximum weight loss of 11 mg in 12% ESP composite at 60% porosity scaffolds was observed in simulated body fluid study. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assay results revealed the absence of toxicity up to 72 h in the composite. 12% ESP showed good cell viability compared to pure PLA and 10% ESP scaffolds having better mechanical and biological properties.

Regulation of cell differentiation via synergistic self-powered stimulation and degradation behavior of a biodegradable composite piezoelectric scaffold for cartilage tissue

The articular cartilage disorder at the junction mainly results from constantly repeated dynamic tension/compression effects with ageing and lack of intrinsic defect repairability. Therefore, the degradable piezoelectric scaffolds are very essential, which mimics the dynamic mechanical loading and optimizes the chondrocyte differentiation during the degradation. Here, a degradable aligned electrospun poly-L-lactic acid (PLLA) modified with graphene (rGO) and polydopamine (PDA) fibrous scaffolds with different orientations (0°, 90°) and surface morphologies (wrinkled and porous) was developed as a biocompatible and degradable piezoelectric scaffold with the self-powered tunable piezoelectricity to modulate cell behaviour and cell differentiation by tuning the degradation effect. The results show that the electrical output and mechanical properties of the composite fibrous scaffold can be improved by adding rGO and applying mechanical force along with the 90° orientation. With changing the degradation behavior, dynamic mechanical loading on the porous PLLA/rGO/PDA fibrous scaffold exhibits a significant increase in cell proliferation and secretion of extracellular matrix (ECM). More surprisingly, as extending the degradation periods to 21 days, a higher glycosaminoglycans (GAGs) synthesis was detected in prechondrogenic ATDC5 cells cultured on the degraded porous scaffold compared with that after 7 days’ culture. This indicated that long-term degradation favoured promoting cell differentiation of ATDC5 towards a chondrogenic phenotype due to dynamic mechanical loading, low-intensity electrical stimulation, and interconnected porous structural morphology. In contrast, on the wrinkled PLLA/rGO/PDA fibre with a high-intensity electrical stimulation, the ALP activity significantly increased after 21 days, inducing mineralization with the differentiation of ATDC5 into osteocytes. The modulation of the degraded environment and electrical stimulation of the piezoelectric scaffold offers an effective alternative to influence cell functions, significantly improving the ECM secretion and cell differentiation.

3D Printing of Collagen/Oligomeric Proanthocyanidin/Oxidized Hyaluronic Acid Composite Scaffolds for Articular Cartilage Repair.

Articular cartilage defects affect millions of people worldwide, including children, adolescents, and adults. Progressive wear and tear of articular cartilage can lead to progressive tissue loss, further exposing the bony ends and leaving them unprotected, which may ultimately cause osteoarthritis (degenerative joint disease). Unlike other self-repairing tissues, cartilage has a low regenerative capacity; once injured, the cartilage is much more difficult to heal. Consequently, developing methods to repair this defect remains a challenge in clinical practice. In recent years, tissue engineering applications have employed the use of three-dimensional (3D) porous scaffolds for growing cells to regenerate damaged cartilage. However, these scaffolds are mainly chemically synthesized polymers or are crosslinked using organic solvents. Utilizing 3D printing technologies to prepare biodegradable natural composite scaffolds could replace chemically synthesized polymers with more natural polymers or low-toxicity crosslinkers. In this study, collagen/oligomeric proanthocyanidin/oxidized hyaluronic acid composite scaffolds showing high biocompatibility and excellent mechanical properties were prepared. The compressive strengths of the scaffolds were between 0.25–0.55 MPa. Cell viability of the 3D scaffolds reached up to 90%, which indicates that they are favorable surfaces for the deposition of apatite. An in vivo test was performed using the Sprague Dawley (SD) rat skull model. Histological images revealed signs of angiogenesis and new bone formation. Therefore, 3D collagen-based scaffolds can be used as potential candidates for articular cartilage repair.

Moxifloxacin-loaded in situ synthesized Bioceramic/Poly(L-lactide-co-ε-caprolactone) composite scaffolds for treatment of osteomyelitis and orthopedic regeneration

High local intraosseous levels of antimicrobial agents are required for adequate long-term treatment of chronic osteomyelitis (OM). In this study, biodegradable composite scaffolds of poly-lactide-co-ε-caprolactone/calcium phosphate (CaP) were in-situ synthesized using two different polymer grades and synthesis pathways and compared to composites prepared by pre-formed (commercially available) CaP for delivery of the antibiotic moxifloxacin hydrochloride (MOX). Phase identification and characterization by Fourier transform infra-red (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) confirmed the successful formation of different CaP phases within the biodegradable polymer matrix. The selected in-situ formed CaP scaffold showed a sustained release for MOX for six weeks and adequate porosity. Cell viability study on MG-63 osteoblast-like cells revealed that the selected composite scaffold maintained the cellular proliferation and differentiation. Moreover, it was able to diminish the bacterial load, inflammation and sequestrum formation in the bones of OM-induced animals. The results of the present work deduce that the selected in-situ formed CaP composite scaffold is a propitious candidate for OM treatment, and further clinical experiments are recommended.

3D-printed biodegradable composite scaffolds with significantly enhanced mechanical properties via the combination of binder jetting and capillary rise infiltration process

For hard tissue engineering applications, biodegradable composite scaffolds have been extensively investigated because of their satisfactory mechanical properties and biocompatibility. Recently, 3D printing processes have received substantial attention in the tissue engineering field because of their ability to be customized for tissues that have suffered different types of loss or damage for each patient. However, previous studies on material extrusion-based techniques lack flexibility in the filler loading amount and cannot fulfill requirements that aim to enhance mechanical properties and biocompatibility. Herein, we propose a biodegradable polymer-based composite scaffolds with high ceramic loadings fabricated using the binder jetting (BJ) technique conjugated with capillary rise infiltration. A calcium sulfate hemihydrate (CSH) scaffold was fabricated using BJ-based 3D printing. Thereafter, CSH was transformed into biphasic calcium phosphate (BCP) using hydrothermal treatment, followed by heat treatment. Melted polycaprolactone (PCL) was infiltrated in the resulting BCP scaffold. BCP was then completely dispersed in the PCL matrix, and the calculated PCL loading in the BCP matrix exceeded 40 vol%. The PCL/BCP composite scaffold demonstrated the highest compressive strength, moduli, and toughness with the fracture mode shifted from brittle to less brittle. Moreover, a stable PCL/BCP surface promotes initial cell responses and shows sufficient proliferation and differentiation of pre-osteoblast cells.

<i>In Vitro</i> Characterization of Polyurethane-Carbon Nanotube Drug Eluting Composite Scaffold for Dental Tissue Engineering Application

Tooth loss due to periodontal disease, dental caries, trauma or a variety of genetic disorders causes an adverse inability in adult’s lives. It is proved that biodegradable composite scaffolds in dental tissue engineering could play crucial role. To inhibit bacterial colonization in dental structure noticeable research concerning the drug delivery approach has been administrated. Nanostructures retain and release drug molecules more efficiently and continuously than other microstructure. In the present research, composite electrospun nanofibers of polyurethane-Single-walled carbon nanotube (SWNT) by the different mass ratios of metronidazole benzoate were prepared. Physico-chemical characterization of scaffolds including Scanning electron microscopy (SEM), uniaxial tensile testing and Ultraviolet-Visible (UV-Vis) spectroscopy analysis was operated. Culture of dental pulp stem cells (DPSCs) to evaluate cells behavior was carried out. The role of nanofiber diameters and drug content on releasing profile of the scaffolds was investigated. The median diameter of the nanofibrous scaffold was reduced from 330 ± 4 to 120 ± 4 nm. Ultimate stress and Young modulus of the scaffolds by enhancement of drug content increased from 0.28 ± 0.05 up to the 1.8 ± 0.05 MPa and 0.87 ± 0.05 up to the 4.4 ± 0.05 Mpa respectively. According to the result, prolonged and continuous releasing profile of the drug molecules was achieved. As the content of the drug increased, the drug was released continuously. It means that two parameters of fiber's diameter and drug ratio affected the releasing behavior of composite structures. Polyurethane-SWNT scaffolds contained metronidazole benzoate presented appropriate support of DPSCs adhesion and proliferation and biomimetic architecture like the structure of dental ECM.

Fabrication and Investigation of the Suitability of Chitosan-Silver Composite Scaffolds for Bone Tissue Engineering Applications

Scaffolds fabricated with only chitosan (CS) as base polymer is limited by its fast degradation rate, reduced mechanical strength and diminished bioactivity. To achieve optimal properties suitable for bone tissue engineering, CS based scaffolds are developed by addition of copolymers, nanoparticles, and functional group modifications. In our study, biodegradable composite scaffolds were fabricated by utilizing CS and silver nanoparticles (AgNPs) were in-situ synthesised on CS matrix with no external reducing agent. The scaffold was investigated for its suitability to be employed in bone tissue engineering (BTE) applications. The scaffolds were found to be highly porous and possess the ability of hydration, adsorb proteins and biomineralization. Chelation with silver ions greatly improved the properties of CS scaffolds by controlling swelling and degradation rate. In addition this, the scaffolds were found to exert broad spectrum antibacterial activity. Furthermore, the scaffolds are highly biocompatible and supported the growth of osteoblast. It also promoted osteogenic differentiation by upregulating Runt-related transcription factor 2 (Runx2), Type-1 collagen (Col-I), Alkaline phosphatase (ALP) activity and secreted Osteocalcin (OC) levels. Among the synthesized scaffolds, CS-Ag 1.5 M scaffold was found to be superior and suitable for bone tissue engineering applications.

An in vitro evaluation of zinc silicate fortified chitosan scaffolds for bone tissue engineering

Tissue engineering aims at replacement, repair, and regeneration of tissues by a combination of scaffolds, growth factors, and cells. In this study, we report the synthesis of biodegradable composite scaffolds fortified with mesoporous zinc silicate (mZS) and assessment of in vitro properties for bone tissue engineering (BTE) applications. The scaffolds consisted of chitosan (CS) incorporated with mZS at 0.1, 0.2, 0.3, and 0.5 wt%. The bio-composite scaffolds were visualized using Field Emission Scanning Electron Microscopy (FE-SEM). The incorporation of mZS was confirmed using Energy dispersive x-ray (EDS) analysis. Biomineralization studies were conducted in simulated body fluid (SBF) and indicated bioactivity of fabricated scaffolds. The scaffolds also displayed antibacterial action against Staphylococcus aureus. Cellular attachment within the scaffold network established biocompatibility of the material. Incorporation of mZS within the chitosan scaffolds matrix improved properties such as porosity, degradation rate, and biomineralization. Therefore, fabricated scaffolds exhibit exceptional features and have the potential to serve as an implant for BTE applications.

Preparation and Characterization of Surface Heat Sintered Nanohydroxyapatite and Nanowhitlockite Embedded Poly (Lactic-co-glycolic Acid) Microsphere Bone Graft Scaffolds: In Vitro and in Vivo Studies.

In the context of using bone graft materials to restore and improve the function of damaged bone tissues, macroporous biodegradable composite bone graft scaffolds have osteoinductive properties that allow them to provide a suitable environment for bone regeneration. Hydroxyapatite (HAP) and whitlockite (WLKT) are the two major components of hard tissues such as bone and teeth. Because of their biocompatibility and osteoinductivity, we synthesized HAP (nHAP) and WLKT nanoparticles (nWLKT) by using the chemical precipitation method. The nanoparticles were separately incorporated within poly (lactic-co-glycolic acid) (PLGA) microspheres. Following this, the composite microspheres were converted to macroporous bone grafts with sufficient mechanical strength in pin or screw shape through surface sintering. We characterized physico-chemical and mechanical properties of the nanoparticles and composites. The biocompatibility of the grafts was further tested through in vitro cell adhesion and proliferation studies using rabbit bone marrow stem cells. The ability to promote osteogenic differentiation was tested through alkaline phosphate activity and immunofluorescence staining of bone marker proteins. For in vivo study, the bone pins were implanted in tibia bone defects in rabbits to compare the bone regeneration ability though H&E, Masson’s trichrome and immunohistochemical staining. The results revealed similar physico-chemical characteristics and cellular response of PLGA/nHAP and PLGA/nWLKT scaffolds but the latter is associated with higher osteogenic potential towards BMSCs, pointing out the possibility to use this ceramic nanoparticle to prepare a sintered composite microsphere scaffold for potential bone grafts and tissue engineered implants.

A silk-based high impact composite for the core decompression of the femoral head.

Core decompression of the femoral head is a recommended head-conserving strategy for early-stage osteonecrosis of the femoral head. However, no ideal filling material has been found so far. In this study, we fabricated a "solid core-porous coating" composite scaffold, which is a silk fibroin/hydroxypropyl methylcellulose (SF/HPMC) scaffold, by a "two-step" process. The solid core scaffold possesses a sufficient compression modulus (860 MPa) for support, while the porous coating scaffold with controllable pore size and porosity provides a suitable microenvironment for the osteoblast cell to adhere and proliferate. Moreover, the porous coating scaffold was mineralized by adding different contents of hydroxyapatite crystal to further enhance its osteoinductivity, according to the simulated body fluid (SBF) biomineralization assay. To demonstrate the biocompatibility and osteoinductivity of such composite scaffolds, a series of in vitro experiments were performed, indicating the MC3T3-E1 pre-osteoblast cells grew and differentiated well on the mineralized porous coating scaffolds. The mechanical testing results also proved that the mechanical property of the solid core scaffold varied (230-1600 MPa) with different solid contents of SF/HPMC, as expected. Furthermore, the rabbit femoral head core decompression model was adopted and confirmed the excellent mechanical performance of the solid core scaffolds, as well as the satisfied osteoinductivity of the porous coating scaffold, by inserting the composite scaffolds into the bone tunnel in vivo. All of the preliminary results implied that the novel biodegradable composite scaffold has an outstanding prospective for the clinical use of core decompression of the femoral head.

Biodegradable nanocomposite fibrous scaffold mediated local delivery of vancomycin for the treatment of MRSA infected experimental osteomyelitis.

There is an increased demand for an ideal biodegradable biomaterial that eradicates infection, while concurrently promoting tissue regeneration in osteomyelitic bone, which eliminates the need for revision surgery. In this study, our objective was to evaluate the efficacy of a nanocomposite fibrous scaffold (silica coated nanohydroxyapatite-gelatin reinforced with poly-l-lactic acid yarns) containing vancomycin for treating methicillin-resistant Staphylococcus aureus (MRSA) induced osteomyelitis in rat models. The antibiotic was either incorporated during scaffold synthesis (SE-V) or loaded directly after the development of the scaffold (SA-V) at 5 wt% and 15 wt%. There was a sustained release of vancomycin from both the groups of scaffolds for 30 days and the released drug demonstrated antibacterial activity against MRSA. Furthermore, implantation of the composite scaffold into osteomyelitic rat femur resulted in significant bacterial reduction, mainly with 15 wt% drug and its efficacy was comparable to that of commercial graft Stimulan. Both drug entrapped and absorbed composite scaffolds promoted bone regeneration in 3 months, with no distinguishable difference between them. However, Stimulan resorbed fast and there were bone voids at the defect site after 3 months. Hence, the nanocomposite fibrous scaffold containing vancomycin can be proposed as a bi-functional graft that can reduce bacterial infection, while subsequently engineer new bone in osteomyelitis.

3D Bioprinting of Novel Biocompatible Scaffolds for Endothelial Cell Repair.

The aim of this study was to develop and evaluate an optimized 3D bioprinting technology in order to fabricate novel scaffolds for the application of endothelial cell repair. Various biocompatible and biodegradable macroporous scaffolds (D = 10 mm) with interconnected pores (D = ~500 µm) were fabricated using a commercially available 3D bioprinter (r3bEL mini, SE3D, USA). The resolution of the printing layers was set at ~100 µm for all scaffolds. Various compositions of polylactic acid (PLA), polyethylene glycol (PEG) and pluronic F127 (F127) formulations were prepared and optimized to develop semi-solid viscous bioinks. Either dimethyloxalylglycine (DMOG) or erythroprotein (EPO) was used as a model drug and loaded in the viscous biocompatible ink formulations with a final concentration of 30% (w/w). The surface analysis of the bioinks via a spectroscopic analysis revealed a homogenous distribution of the forming materials throughout the surface, whereas SEM imaging of the scaffolds showed a smooth surface with homogenous macro-porous texture and precise pore size. The rheological and mechanical analyses showed optimum rheological and mechanical properties of each scaffold. As the drug, DMOG, is a HIF-1 inducer, its release from the scaffolds into PBS solution was measured indirectly using a bioassay for HIF-1α. This showed that the release of DMOG was sustained over 48 h. The release of DMOG was enough to cause a significant increase in HIF-1α levels in the bioassay, and when incubated with rat aortic endothelial cells (RAECs) for 2 h resulted in transcriptional activation of a HIF-1α target gene (VEGF). The optimum time for the increased expression of VEGF gene was approximately 30 min and was a 3-4-fold increase above baseline. This study provides a proof of concept, that a novel bioprinting platform can be exploited to develop biodegradable composite scaffolds for potential clinical applications in endothelial cell repair in cardiovascular disease (CVD), or in other conditions in which endothelial damage occurs.

Fabrication of bimodal open-porous poly (butylene succinate)/cellulose nanocrystals composite scaffolds for tissue engineering application

The design of porous tissue engineering scaffold with multiscale open-pore architecture (i.e., bimodal structure) promotes cell attachment and growth, which facilitates nutrient and oxygen diffusion. In this study, a porous poly (butylene succinate) (PBS)/cellulose nanocrystals (CNCs) composite scaffold with a well-defined controllable bimodal open-pore interconnected structure was successfully fabricated. The bimodal open-porous scaffold architecture was designed by synergistic control of temperature variation and a two-step depressurization in a supercritical carbon dioxide (Sc-CO2) foaming process. The microstructure and properties of the bimodal open-porous PBS/CNCs scaffold, such as morphology, open porosity, hydrophilic and degradation performance, and mechanical compression properties, were analyzed. In the experiments, the scaffold with unimodal pore structure was used for comparison. The results showed that the bimodal open-porous PBS5 scaffold displayed a well-defined bimodal open-pore structure composed of large pore (~68.9 μm in diameter) and small pore (~11.0 μm in diameter), with a high open porosity (~95.2%). In addition, the scaffolds exhibited good mechanical compressive properties (compressive strength of 2.76 MPa at 50% strain), hydrophilicity (water contact angle of 71.7 °C) and in vitro degradation rate. Moreover, in vitro biocompatibility was determined with NIH-3T3 fibroblast cells using MTT assay and live/dead cell viability assay. Results indicated that the obtained bimodal open-porous scaffolds had a good biocompatibility and the viability of cells grown on the scaffolds reached up to 98% after 7th day of culture. Therefore, our work provides new insights into the use of biodegradable polymeric composite scaffolds with bimodal open-pore structure and balanced properties in tissue engineering.